Knockouts of sulfur metabolism genes induce chronic inflammation and immune dysregulation in Drosophila melanogaster

ABSTRACT: In this study, we examined a unique collection of Drosophila melanogaster strains with knockouts of three key genes involved in H₂S synthesis and metabolism, with the aim of elucidating the role of this adaptive system in immunity. Genetic disruptions in sulfur metabolism—specifically, combined deletions of the cbs, cse, and tst1 genes—lead to reduced H₂S levels and hyperhomocysteinemia in flies. These metabolic changes induce oxidative stress and trigger chronic inflammatory responses. Transcriptomic analysis and q-PCR revealed significant activation of major immune pathways, including IMD, Toll, and Jac-Stat. A septic injection of Bacillus subtilis induces increased expression of antimicrobial peptides (AMPs) and pattern recognition receptors in knockout flies. Notably, double- and triple-knockout strains exhibit prolonged immune activation. The triple knockout exhibits the worst survival rate following septic injury induced by Bacillus subtilis. These results highlight the critical role of H₂S in modulating innate immunity and suggest that sulfur metabolism is an important regulator of inflammatory homeostasis in Drosophila.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE333980 | GEO | 2026/06/06

REPOSITORIES: GEO